WO1995013760A1 - Dispositif a diffusion controlee mu par gaz - Google Patents

Dispositif a diffusion controlee mu par gaz Download PDF

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Publication number
WO1995013760A1
WO1995013760A1 PCT/AU1994/000701 AU9400701W WO9513760A1 WO 1995013760 A1 WO1995013760 A1 WO 1995013760A1 AU 9400701 W AU9400701 W AU 9400701W WO 9513760 A1 WO9513760 A1 WO 9513760A1
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WO
WIPO (PCT)
Prior art keywords
chamber
controlled release
gas
release device
egress
Prior art date
Application number
PCT/AU1994/000701
Other languages
English (en)
Inventor
Peter Costigan
Keith James Ellis
Ralph Henry Laby
Bruno Kautzner
Warren Goodwin Chandler
Original Assignee
Commonwealth Scientific And Industrial Research Organisation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from AUPM6103A external-priority patent/AUPM610394A0/en
Application filed by Commonwealth Scientific And Industrial Research Organisation filed Critical Commonwealth Scientific And Industrial Research Organisation
Priority to AU81356/94A priority Critical patent/AU8135694A/en
Publication of WO1995013760A1 publication Critical patent/WO1995013760A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
    • A61M31/002—Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
    • A61D7/00—Devices or methods for introducing solid, liquid, or gaseous remedies or other materials into or onto the bodies of animals

Definitions

  • This invention relates to controlled release devices adapted to contain material, eg a solid liquid or paste material, and to release it over an extended period of time.
  • material eg a solid liquid or paste material
  • Such devices are used, for example in pharmaceutical and veterinary applications, and the materials may comprise or contain therapeutic or prophylactic drugs, nutrients or dietary supplements, or other biologically active substances.
  • a well established application of such devices is for intra-ruminal administration of various agents to ruminants.
  • the present application primarily discusses improved devices for these applications, but it is emphasised that the concepts of the invention are adaptable not only to ruminant husbandry and medication but also in the general field of animal and human medicine.
  • the device of the present invention may be employed as a controlled release device for use in the general environment or in industrial processes.
  • a gas-tight plunger and a gas-permeable membrane are used to augment spring control of the release rate of the material from the device. Gas is allowed to permeate from the external environment into the tubular body behind the plunger and thereby can limit the rate at which the plunger can move under the influence of the helical spring.
  • United States patent 5198222 to Scully et al describes a time-release bolus containing a breakable plastic capsule or bag containing a fluorocarbon gas under pressure. Immediately prior to insertion of the bolus per os, the tubular body is squeezed to rupture this plastic capsule, which action releases gases into a sealed internal chamber. These gases exert pressure on a further inner container whose contents are thereby urged, over a period of time, through an exit orifice. The duration of this period is not specified but is thought by the present applicant to be likely to be relatively short, in view of the diminishing pressure of the internal chamber as it expands with release of the contents.
  • the invention essentially entails the concept of providing for differential permeability of one or more selected gases contained within a controlled release device relative to one or more gases of its external environment when in situ, whereby to provide a sustained gas pressure drive for controlled release of contained material over an extended period of time. It was realised by the present inventors that, with some configurations of device according to the aforementioned patent 558009, when installed in a rumen, carbon dioxide diffused into the device so rapidly compared to the efflux of oxygen and nitrogen outwardly, that there was a short-term increase in the total gas pressure behind the spring-loaded plunger before the movement of the plunger brought about the volume increase and accompanying pressure limitations.
  • a controlled release device adapted to contain a material and to release it over an extended period of time.
  • the device includes a hollow body adapted to contain the material, and egress means in the body adapted to allow egress of the material.
  • Means for urging the material towards the egress means for egress therefrom includes an expandable chamber in the body separated from the environment external to the body by gas-permeable partition means.
  • This gas-permeable partition means is arranged to be differentially permeable for selected gases in the chamber and the extemal environment, whereby the gas pressure in the chamber increases above and is maintained above a level sufficient to produce a driving force for sustaining egress of said material over the extended period of time.
  • the gas permeable partition means may comprise a wall segment of the body, for example a membrane.
  • the membrane is preferably a polymer selected from the group comprising polyethylene, polypropylene, polyester, polyvinylidene chloride and poly(dimethylsiloxane), and is advantageously a metallised laminate of such a polymer.
  • a low-polarity polymer may be preferred in some cases.
  • the urging means may alternatively or further include flexible sheet means about the chamber and expandable by the gas pressure as the material is released from the body over the extended period of time.
  • this flexible sheet means may be associated with a wall segment or membrane forming the gas permeable partition means.
  • the flexible sheet means may enclose the chamber and comprise the gas permeable partition means. In this case, there may be a separate opening through the body or the body may simply be of a material permeable in a non- differential or less differential manner with respect to the selected gases.
  • the urging means may include slidable plunger means which may be in contact with the material and may, for example separate the aforementioned chamber from a space adapted to contain the material. Depending upon the embodiment, this plunger means may be in gas-tight slidable engagement with an internal wall of the body.
  • the chamber may further contain a substance adapted to generate a vapour within the chamber, at least when the device is in situ, to provide an additional partial gas pressure in the chamber and thereby to provide the potential for further inward gas permeation from the environment.
  • This vapour preferably has a vapour pressure less than one atmosphere at the temperature of the extemal environment within which the device is to be sited in use and may be selected from a suitable volatile substance.
  • Possible such substances include methanol and other alcohols, acetonitrile, ammonia, acetic acid, a subliming substance such as iodine, or a carrier liquid or solid material (eg cyclodextrins) in which a gas can be dissolved or otherwise retained under some circumstances but which would be released in the environment of application.
  • the device may comprise pressure setting means operable to increase the gas pressure in the chamber prior to administration of the device and thereby to provide the potential for further inward gas permeation from the environment.
  • This pressure setting means may comprise structure carried by the body and adjustable to compress the chamber and thereby reduce its volume and increase its contained gas pressure.
  • a still further alternative comprises port means to draw in gas as the chamber is cooled, which port means is then sealable so that the gas pressure increases significantly at the in situ temperature.
  • the controlled release device further includes means to vary the geometry of the device between a first configuration permitting administration or dosing of the device to an operating location and a second configuration adapted to facilitate retention of the device at the location.
  • the invention also provides a method of delivering a composition to a ruminant over an extended period of time comprising: administering per os a controlled release device containing said composition to the rumen of the ruminant, allowing one or more of the gases in the rumen to permeate into a chamber of the device whereby gas pressure in said chamber in increased above and maintained above a level sufficient to produce a driving force for sustaining egress of said composition into the rumen over said extended period of time.
  • the invention provides a controlled release device adapted to contain a material, eg a solid, liquid or paste material, and to release it over an extended period of time, the device comprising: a hollow body adapted to contain the material; egress means in the body adapted to allow egress of the material; and means for urging the material towards the egress means for egress therefrom, the means including an expandable chamber in the body; and a substance in the chamber adapted to at least partially vaporise within the chamber, at least when the device is in situ, to thereby increase and maintain the gas pressure in the chamber above a level sufficient to provide a driving force for sustaining egress of the material over said extended period of time.
  • a material eg a solid, liquid or paste material
  • a controlled release device adapted to contain a material, eg a solid, liquid or paste material, and to release it over an extended period of time, the device comprising: a hollow body adapted to contain the material; egress means in the body adapted to allow egress of the material; and means for urging the material towards the egress means for egress therefrom, such means including an expandable chamber in the body; and means adaptable, prior to administration of the device, to increase the gas pressure in the chamber above that outside the body and to thereby provide a driving force for sustaining egress of the material over the extended period of time.
  • a material eg a solid, liquid or paste material
  • said means to increase the gas pressure comprises structure carried by said body and adjustable to compress said chamber and thereby reduce its volume and increase its contained gas pressure.
  • said means to increase the gas pressure comprises means to introduce a gas into said chamber from outside said body to increase the gas pressure therein above that outside the body.
  • a still further alternative for the pressure increasing means comprises port means to draw in gas as the chamber is cooled, which port means is then sealable so that the gas pressure increases significantly at the in situ temperature.
  • Figure 1 is a diagrammatic axial cross-sectional view of a controlled release device in accordance with a first embodiment of the invention, suitable for administering therapeutic and other agents in the rumen of a ruminant;
  • Figure 2 is a similar view of a modified form of the device illustrated in Figure 1 and additionally containing a volatile substance;
  • Figure 3 is a similar view of a further embodiment of the invention which also incorporates an arrangement for pre-loading the gas pressure chamber, the device being shown in its transport and storage condition prior to administration;
  • Figure 4 is a view corresponding to Figure 3 but depicting the device in its loaded condition ready for administration;
  • Figures 5 and 6 are views similar to Figures 3 and 4 respectively of a still further embodiment of the invention.
  • FIGS 7 to 10 depict the results of various experiments utilising devices of the form depicted in Figures 5 and 6.
  • the controlled release device 10 depicted in Figure 1 is an experimental device for use in rumen f ⁇ stulated cattle.
  • the device 10 includes a hollow body formed from a disposable polypropylene hypodermic syringe barrel 11 which has the usual flange 12 at its open end 13 and a nozzle 14 at the other end.
  • Nozzle 14 serves as restricted egress means which allows egress of therapeutic material 9 housed within barrel 11 adjacent nozzle 14.
  • the therapeutic material is depicted in this case as a packed powder, paste, or the like and would typically consist of an active constituent in a rratrix chosen to facilitate subsequent delivery of the active constituent from the barrel.
  • Means 20 is provided for urging material 9 towards nozzle 14 for egress therefrom.
  • This means 20 includes an expandable chamber 22 defined by a suitable substantially impermeable flexible sheet means such as metallised laminate film 19 and separated from the extemal environment by a gas- permeable partition provided by a diaphragm or membrane 16.
  • Membrane 16 is clamped to flange 12 by means of a pair of clamping rings 17,18 to provide a gas-tight seal around the flange 12 and membrane 16. Rings 17,18 are held together by any suitable means, for example screws (not shown).
  • Film 19 is in the shape of an open bag and is sealed at the mouth of the bag to the inner rim of barrel 11 adjacent flange 12 by an internal sealing ring 24.
  • Membrane 16 is selected to be differentially permeable with respect to the principal gases of the extemal environment and in chamber 22 so that the gas pressure in the chamber increases above and is maintained above a level sufficient to produce a driving force for sustaining egress of therapeutic material 9 from outlet 14 over the extended period of time for which the device 10 is expected to release its contents.
  • membrane 16 is selected to be more permeable with respect to carbon dioxide and/or methane, the principal gases of the rumen, than oxygen and/or nitrogen, the principal components of the air with which chamber 22 is initially charged.
  • Suitable membrane materials especially for an aqueous environment, are the polymers such as polyethylene, polypropylene, poly(dimethyl siloxane), polyester and polyvinylidene chloride.
  • the composition may progressively soften and be urged through the outlet and be wiped clear.
  • the driving force applied by the pressurised chamber 22 retains the composition in contact with the restricted outlet, thereby preventing rumen-derived solids from entering the device and tending to act as a barrier to excessive degradation. In this way, the device provides an approximately uniform rate of delivery of the therapeutic material.
  • the rates of permeation are determined by the characteristics and dimensions of the gas-permeable partition and the permeability coefficients of the gases.
  • the reported permeability coefficients for the gases in question at 39°C (a typical interior rumen temperature) across a polypropylene membrane are approximately in the ratio 1:4:2:16 in the order nitrogen:oxygen:methane:carbon dioxide. These are for an ideal system but are thought to indicate the general relative relationship for the device in a real rumen environment. Under working conditions, the increasing volume as the material is dispensed serves to enhance the relative differences between the permeabilities of the gases entering the chamber and permeating out of the chamber.
  • the time that the gas pressure remains at or above "operational pressure" ie a pressure within chamber 22 exceeding the intra-rumen pressure acting at outlet nozzle 14, is determined by the permeability characteristics of the membrane, by the volume of gas in chamber 22, and by the rate of increase in the initial volume and composition of chamber 22 caused by the dissolution and disappearance of the material at the outlet nozzle 14. It will thus be appreciated that the slow permeation of the gases exercises a control over the delivery of the therapeutic material, and that the rate and duration of this control is also determined by selection of the above-mentioned parameters. Selection of the parameters in turn depends on the particular application and on the nature of the particular material to be dispensed. In the latter case, for example, the nature of the material will influence the driving force required.
  • the device 10 may be used in other applications by appropriate selection of the permeability characteristics of the membrane 16, the volume and composition of the gas within chamber 22, the rates of volume and pressure change in volume 22, and the composition of the external environmental gas.
  • device 10 is desirably fitted with means to vary its geometry between a first configuration permitting administration of the device to the rumen, and a second configuration adapted to facilitate retention of the device in the rumen, ie to reduce the risk of regurgitation.
  • Suitable such means are disclosed in the aforementioned Australian patents 520409 and 558009, or in Australian patent application 47162/85, or in US patent 3844285.
  • flexible film 19 is ideally made of a gas impermeable film, for example a suitable metallised polymer or proprietary laminate with one or more impermeable layers.
  • film 19 is in the form of an unfolding soft bag.
  • the bag does not need to slide along the inner wall of barrel 11 thereby causing frictional drag, which might otherwise impair movement of the bag since the degree of contact of the bag with the inside wall of barrel 11 would depend on the internal vapour pressure.
  • the film 19 may be provided in the form of a stretchable material, provided the permeability does not significantly alter as it stretches, or of a folded rigid rib bag. This construction offers the advantage that the bag may be made of laminated plastics which will be of heavier wall thickness and thereby reduce the gradual permeation of drive gas from within chamber 22.
  • a suitable volatile substance is methyl alcohol (CH 3 OH).
  • This substance provides an additional vapour pressure within chamber 22'.
  • methyl alcohol vapour permeates through membrane 16' as has been demonstrated by its gradual loss from an experimental device.
  • Appropriate choice of volatile substance 30 and membrane 16' would allow for optimum selectivity and result in a lower rate of loss of the vapour and thereby enhance the medium to long-term pressure within chamber 22' arising from the inward permeation of, eg carbon dioxide and methane, and thus the lifetime of the device.
  • the small volume of volatile substance within chamber 22 serves to maintain a partial pressure gradient for the extemal gases downward into chamber 22'.
  • the vapour pressure of the volatile substance 30' remains constant at constant temperature, the partial pressure will also remain constant despite the steady increase in volume, thus reducing the partial pressures of the other gas components within the chamber.
  • a partial pressure gradient downward into the chamber is established for extemal gases while volatile substance remains in the chamber. While these conditions apply, the total pressure in chamber 22' exerts positive drive to the therapeutic material 9'.
  • the volatile substance has a vapour pressure of less than one atmosphere at the temperature of the environment within which the device is to be used.
  • the volatile substance should have no adverse effects on the gas permeable partition, ie membrane 16' in this case, and film material.
  • the permeation loss through the membrane of the volatile substance should be low in order to minimise its loss over time from the device.
  • choice of a volatile substance which in its liquid state has a polarity contrasting with that of the membrane and device materials is particularly desirable.
  • common low polarity plastics such as polyethylene, and polypropylene will retain highly volatile liquids such as methanol (methyl alcohol) or acetonitrile preferentially. Methanol and the other volatile alcohols are the preferred liquids when low-polarity components are used in the device 10'.
  • the rumen gases permeating into chamber 22' cause a dilution of the vapour generated by substance 30 and therefore more of the volatile substance must vaporise so as to maintain the partial vapour pressure of the substance constant.
  • the device falls into two operational groups depending on the state of the therapeutic material 9' (ie the payload) it may contain:-
  • this device preferably includes a non-return valve at outlet 14' so as to eliminate the effect of minor fluctuations in rumen gas pressure.
  • a non-return valve at outlet 14' so as to eliminate the effect of minor fluctuations in rumen gas pressure.
  • FIGS 3 and 4 illustrate a further embodiment 110 of the invention which differs from the earlier described embodiments in a number of respects.
  • a tubular barrel 111 there is again a tubular barrel 111.
  • the therapeutic material is provided in the form of tablets 109a and is delivered through a restricted forward outlet nozzle 114.
  • the rear end of barrel 111 is closed by an end wall I l ia and the chamber 122 comprises a rear portion of the interior of the barrel completed by a lubricated, gas-tight and gas impermeable rubber plunger 119 formed of similar elastomeric material to the septa used in evacuated blood collection tubes and of similar construction to a disposable syringe plunger.
  • the plunger is made gas-tight by deforming it for insertion into the barrel.
  • the gas-permeable partition means 116 is provided by appropriate choice of the material of barrel 111, to achieve the required differential permeation characteristics together with the necessary rigidity, eg a solid plastics such as polypropylene, polyethylene, or polyvinylchloride.
  • the barrel can be coated internally with an appropriate material, eg a metallised polymer such as a metallised polyester or a coating of polyvinylidene chloride (saran), to produce the required differential permeation characteristics.
  • the configuration for pre-charging chamber 122 before administration of the device is provided by forming outlet orifice 114 in a separable snap-on cap 150 which has a cylindrical rim 151 defining a socket with peripheral shallow ribs 152. These ribs are designed to snap over and behind a matching pair of ribs or shallow lug rings 153 on the outside of the open end of barrel 111.
  • Device 110 is assembled with its tablets for transport by having the set of tablets 109a project beyond the barrel and retaining cap 150 on the last tablet with a plastic shrink-wrap 155 ( Figure 3). Water soluble adhesive is placed on the outside surface of the plunger 120 and between each of the tablets 109a containing the active compound so that the plunger, tablets and cap 150 form an integral unit.
  • Shrink-wrap 155 is provided to maintain the integrity of the assembly during shipping, handling and storage The gluing of the tablets into an integral core prevents or at least minimises permeation of gas between the tablets during storage.
  • cap 150 is snapped onto the end of the barrel to achieve the configuration shown in Figure 4. This is done either by pushing the cap and barrel together manually or with the aid of a caulking type gun or with the actual dosing gun so that dosing cannot be formed without assembly and pressure pre-loading.
  • the shrink- wrap 155 is then removed.
  • the process of connecting cap 150 to the barrel 111 results in the plunger 122 moving down the barrel, reducing the volume of chamber 122 and increasing the air pressure in the chamber by an amount determined by the initial positioning of plunger 119.
  • the air in the chamber is therefore at an increased predetermined pressure surrounded by a relatively gas impermeable plunger and metallised polyester.
  • the chamber 122 will now behave akin to chamber 22 in the embodiments of Figures 1 and 2.
  • Figures 3 and 4 include a schematic representation at 160 of geometry varying collapsible wings.
  • Figures 5 and 6 depict a still further embodiment 110' in which a compressible telescopically mounted cap 150' is provided at the rear end of the barrel rather than at the outlet end.
  • chamber 122' is defined by a ribbed flexible bag 119' of a differentially gas-permeable material. This bag is wholly sealed closed and is disposed between the rear-most tablet and the head of cap 150' slidably disposed about barrel 111'.
  • Cap 150' has an internal rib 152' at its mouth and is movable between an extended condition determined by an extemal rib 153' at the rear end of the barrel and an inward position ( Figure 6) defined by a peripheral groove 157 on the barrel.
  • Figure 5 shows the situation as the cap is half-way from its fully extended to its pre-load position.
  • the embodiment of Figure 5 and 6 also differs from the previous embodiments in that flexible bag 119' constitutes the gas-permeable partition means corresponding to the membrane 16 of the embodiments of Figures 1 and 2 and the rear part 116 of the barrel itself in the embodiment of Figures 3 and 4.
  • the barrel and cap are formed in a material which is highly and non-differentially permeable, or less differentially permeable, with respect to the principal extemal and internal gases, at least to an extent sufficient to ensure that the bag controls the relative gas flows.
  • Bag 119' should be formed from materials generally similar to the gas permeable partitions of the other embodiments, but having regard to the requirement for both strength and flexibility. The pressure required within the chamber initially will depend on the desired rate and duration of material pay-out.
  • the pressure must also remain sufficiently positive to overcome the frictional resistance of the walls on the plunger. This should amount to no more than a maximum of 20mm of Hg.
  • the maximum pressure required in the chamber for any current commercial active would not exceed two atmospheres. This pressure is easily achievable by finger compression of the plunger and would not place excessive strain on existing hardware.
  • a pressure pre-load can also be produced within the gas bag or chamber by the incorporation of a silicon mbber septum into the closed end of the barrel and in the bag.
  • a gas cylinder incorporated into the device used to administer the CRD to animals could inject a predetermined amount of gas through the septum.
  • FIG. 7 shows the change in plunger position with time for in vivo delivery of chromic oxide capsules to the rumen of cattle utilising a device similar to that of Figures 5 and 6.
  • the membrane bag used was a laminated bilayer of metallised polyester and the gas drive chamber initially occupied about 45% of the intemal volume of the device.
  • Each bag was pre-loaded to 1.45 atmospheres. There is reasonably good linearity with some loss of linearity with most experiments at the upper end of the trial period of 28 days. The result is nevertheless clearly better than that observed in a corresponding experiment with spring-driven devices.
  • Figure 8 compares change in total pressure with time for a device of the type depicted in Figures 5 and 6, for bag materials of different construction, when placed in a similar carbon dioxide atmosphere with a similar bag chamber atmosphere of air plus a major component of chlorodifluoromethane [CHC1F 2 ] from a volatile deposit. These curves demonstrate the different driving pressure profile achievable according to the choice of gas permeable partition.
  • Figure 9 is a similar curve but for different mixes of gases in the drive gas chamber.
  • the bag is of laminated metallised polyester, the bottom curve case in Figure 8. Again the curves demonstrate how different pressure profiles are available according to the choice of gas mixture and vapour pre-load in the pressure drive chamber.
  • Figure 10 compares plunger travel with time for two devices of the type shown in Figures 5 and 6 (A,B) with two devices which are similar save that they have a conventional spring drive rather than a gas pressure drive (C,D).
  • the former exhibits a high level of sustained linearity.
  • Solid s, pastes and liquids can all be delivered utilising devices in accordance with the invention.
  • the device When the device is used with liquids it may be desirable to include a non ⁇ return or one-way valve at the liquid egress port.
  • the egress opening may be designed for either direct expulsion of the material therefrom or for holding the material for dissolution.
  • the actual permeability of these gases may be zero, ie the gas-permeable partition means in question may be totally impermeable, for example to air or one of its components, or substantially so. Such a partition material would be of optimum shelf-life prior to dosing.
  • the invention is highly versatile in adaptability to different applications.
  • a long-term tablet composition with a high payload of active material may require a relatively high pre-load and a relatively high sustained gas pressure, and therefore a high differential permeability.
  • a matrix for an organism eg worm larvae
  • a matrix for an organism may necessarily be a low viscosity aqueous solution, a syrup or a paste, necessitating a relatively small pre-load and a sustained relatively small operating pressure, and a relatively low differential permeability. Either situation can be readily catered for by appropriate choice of the adjustable parameters including gas-permeable material, volume and pressure of the drive chamber, and pre-loading technique.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Hematology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Anesthesiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)

Abstract

Un dispositif à diffusion contrôlée, conçu pour contenir un matériau et le libérer sur une période prolongée, comporte un corps (11) creux recevant ce materiau et un système (14) de sortie placé sur ce corps pour permettre la sortie du matériau. Un système, qui pousse le matériau vers le système de sortie pour l'en faire sortir, comporte une chambre (22) extensible placée dans le corps et séparée de l'extérieur du corps par une cloison (16, 116, 119') perméable aux gaz conçue pour une perméabilité différente selon des gaz choisis, présents dans la chambre et à l'extérieur. La pression de gaz régnant dans la chambre augmente jusqu'à se maintenir au-dessus d'un niveau suffisant à produire une force d'entraînement permettant la sortie du matériau sur une période prolongée.
PCT/AU1994/000701 1993-11-15 1994-11-15 Dispositif a diffusion controlee mu par gaz WO1995013760A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU81356/94A AU8135694A (en) 1993-11-15 1994-11-15 Gas driven controlled release device

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AUPM242993 1993-11-15
AUPM6103A AUPM610394A0 (en) 1994-06-06 1994-06-06 Gas driven controlled release device

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WO1995013760A1 true WO1995013760A1 (fr) 1995-05-26

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999029259A1 (fr) * 1997-12-05 1999-06-17 Dec Research Ameliorations apportees a des dispositifs d'administration et a leur utilisation
WO2001012101A1 (fr) 1999-08-18 2001-02-22 Interag Administration de produits multiples
CN107969348A (zh) * 2017-12-04 2018-05-01 徐州果姿电子商务有限公司 一种畜牧养殖幼崽喂食装置
CN108175926A (zh) * 2017-12-29 2018-06-19 韩培培 一种新型泌尿外科用尿道给药器
CN109260582A (zh) * 2018-11-28 2019-01-25 陈巧丽 一种***或***的药膏均匀涂抹装置
CN109276800A (zh) * 2018-11-28 2019-01-29 陈巧丽 一种***或***的药膏均匀涂抹管

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US4203441A (en) * 1978-12-18 1980-05-20 Alza Corporation Osmotically triggered device with gas generating means
AU1163983A (en) * 1982-02-16 1983-08-25 Commonwealth Scientific And Industrial Research Organisation Gas diffusion controlled release device
EP0091621A1 (fr) * 1982-04-05 1983-10-19 Milliken Research Corporation Pompe à débit lent et constant
EP0250083A2 (fr) * 1986-06-19 1987-12-23 Alza Corporation Forme de dosage avec des moyens pour commander le taux de formation de gaz
WO1991000753A1 (fr) * 1989-07-12 1991-01-24 Apcis Dispositif de delivrance d'un principe actif pharmacologique par pompage electrolytique
WO1994001165A1 (fr) * 1992-07-13 1994-01-20 Elan Medical Technologies Limited Dispositif d'administration de medicaments

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4203441A (en) * 1978-12-18 1980-05-20 Alza Corporation Osmotically triggered device with gas generating means
AU1163983A (en) * 1982-02-16 1983-08-25 Commonwealth Scientific And Industrial Research Organisation Gas diffusion controlled release device
EP0091621A1 (fr) * 1982-04-05 1983-10-19 Milliken Research Corporation Pompe à débit lent et constant
EP0250083A2 (fr) * 1986-06-19 1987-12-23 Alza Corporation Forme de dosage avec des moyens pour commander le taux de formation de gaz
WO1991000753A1 (fr) * 1989-07-12 1991-01-24 Apcis Dispositif de delivrance d'un principe actif pharmacologique par pompage electrolytique
WO1994001165A1 (fr) * 1992-07-13 1994-01-20 Elan Medical Technologies Limited Dispositif d'administration de medicaments

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999029259A1 (fr) * 1997-12-05 1999-06-17 Dec Research Ameliorations apportees a des dispositifs d'administration et a leur utilisation
US6450991B1 (en) 1997-12-05 2002-09-17 Interag Delivery devices and their use
WO2001012101A1 (fr) 1999-08-18 2001-02-22 Interag Administration de produits multiples
US7083590B1 (en) 1999-08-18 2006-08-01 Interag Multiple material dispensing
CN107969348A (zh) * 2017-12-04 2018-05-01 徐州果姿电子商务有限公司 一种畜牧养殖幼崽喂食装置
CN108175926A (zh) * 2017-12-29 2018-06-19 韩培培 一种新型泌尿外科用尿道给药器
CN108175926B (zh) * 2017-12-29 2021-02-23 鄂东医疗集团市中心医院(市普爱医院、湖北理工学院附属医院) 一种新型泌尿外科用尿道给药器
CN109260582A (zh) * 2018-11-28 2019-01-25 陈巧丽 一种***或***的药膏均匀涂抹装置
CN109276800A (zh) * 2018-11-28 2019-01-29 陈巧丽 一种***或***的药膏均匀涂抹管
CN109276800B (zh) * 2018-11-28 2020-12-22 辛佳凌 一种***或***的药膏均匀涂抹管
CN109260582B (zh) * 2018-11-28 2021-07-27 湖南省妇幼保健院 一种***或***的药膏均匀涂抹装置

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